P2‐152: Molecular mapping of Alzheimer's disease: Imaging mass spectrometry

Limited information is available regarding the in-tact human tissue analysis of patients with Alzheimer's Disease (AD). This project focuses on the comparative analysis of formalin-fixed, paraffin-embedded human hippocampal brain tissue from AD patients and healthy patients, as well as mapping the chemical composition of the tissue for the plaques and tangles associated with the onset of the disease. In addition, this project involves the mass spectrometric analysis of purified amyloid plaques extracted from AD brains. We employ advanced imaging mass spectrometry (IMS) technology utilizing matrix-assisted laser desorption/ionization (MALDI) and time-of-flight (TOF) mass spectrometry to provide the first quantitative analysis of AD lesions. This enables a better understanding of the molecular composition of the plaques and tangles associated with the onset of AD in situ. Further, using the optimized sample preparation steps and the imaging technology, we will be able to determine if there are regional variations in the makeup of the plaques and tangles which cannot be determined from optical microscopy. Our preliminary results have demonstrated this technique's usefulness for the comparison of diseased versus normal tissue at a molecular level while maintaining topological and morphological integrity. From the observed peptide clip masses we have established preliminary molecular identifications of the amyloid-beta proteins known to be prominent in the brains of those with AD. We have also identified the amyloid-beta proteins in the extracted amyloid plaque after developing a method for preparing the aliquot for analysis directly on a glass slide. While the mapping of tissue can be done to some extent using microscopy, this imaging technique allows for the concurrent mass mapping and compound identification for any spot on the tissue without disrupting the morphology of the sample. These results will aid in further investigation into the mapping of tissue and identification of protein sequences prevalent in the brains of those with AD. The potential for quantitative analysis of tangles and plaques within AD tissue will further aid in the diagnosis and treatment of the disease.